In this Phase II NIH SBIR, Piezo Resonance Innovations will further optimize and test the Portable Transdermal Patch (PTP) - a needle-free platform delivery technology for drugs and vaccines that are currently delivered subcutaneously. The portable, 200gm (7oz) electronically-controlled transdermal patch for Enfuvirtide delivery employs a patented transducer technology with integrated battery driven controls to deliver drugs as prescribed. The low power of the PTP transducers will open 25 to 125 5m micro-channels in the stratum corneum, without causing long-term skin damage. Thirty-three million people worldwide are living with the Human Immunodeficiency Virus (HIV). Currently, patients infected with HIV receive Highly Active Antiretroviral Therapy (HAART) for the management of the infection. Medication regimens for the management of HIV must be taken with near-perfect compliance to maximize benefits and prevent development of viral resistance. Enfuvirtide, approved by the Food and Drug Administration in 2003, is an infusion inhibitor that blocks the HIV from attaching to the CD4 cell. It is subcutaneously injected twice daily and directed at patients not responding to other treatments. The major side effect is an injection site reaction, which reduces patient compliance substantially. A needle-free device that enhances patient compliance with Enfuvirtide, and other large-molecule medication regimes, like insulin, will be of great benefit. Phase I developed and tested prototypes and met all of the Specific Aims. Transdermal delivery of Enfuvirtide was demonstrated in pig skin models. Reviews by practicing clinicians were positive and have been used to guide the Phase II Beta prototype design requirements. Phase II will optimize the PTP performance characteristics and electronic control into a small lightweight, ergonomic patch. Safety and efficacy of the PTP will then be evaluated in a live animal model. The PTP Transdermal Delivery Technology will: Deliver Enfuvirtide (T-20) Transdermally, increasing patient regime compliance Eliminate the injection site reaction that limits T-20 adoption Act as a platform technology to deliver other large molecule medications (e.g. insulin) Be comfortable to wear, painless during operation, and hide discretely under clothing. Deliver medications through a prescription reservoir that holds dosing for multiple days. Deliver lower dose, sustained delivery - rather than large bolus dosage.